1. Field of the Invention
The invention relates to a conductive surface structure for influencing suspended microscopic particles and cells. It also relates to the use of said structure for controlling the adhesion of the particles and cells.
2. Prior Art
In medical technology, biocompatibility research, especially in the production of transplantable materials but also in biological-pharmacological research for a long time, surfaces have been sought with repelling effects on particles and cells in physiological and technical solutions on the one hand but which in certain cases promote adhesion (BOGRAND, P. (ed.), Physical Basis of Cell-Cell-Adhesion, CRC Press, Inc., Boca Raton, Fla., 1988. CURTIS, A. S. G., PITTS, J. D. (eds.), Cell Adhesion and Motility, Cambridge University Press, Cambridge, 1980. GRINELL, F., Int. Rev. Cytol, 53:65-144, 1978. LEE, L. H., Recent Advances in Adhesion, Gordon & Breach, London, 1973. OTTEWILL, R. H., ROCHESTER, C. H., SMITH, A. L. (eds.), Adsorption from Solution, Academic Press, London. PERELSON, A. S., DeLISI, Ch., WIEGEL, F. W., Cell Surface Dynamics, Concepts and Models, Marcel Dekker, Inc., New York, Basel, 1984). As a rule this "surface modification" is achieved by hydrophilization or hydrophobization, via the attachment of charged molecular groups or by local attachment of highly specific bonding sites (e.g., antibodies). The disadvantage of these surface modifications is their small reach in the particle suspension (generally a few .ANG.), the extremely variable long term stability and the absence of controllability of the effect.
The fact that electrical fields can be decoupled via electrodes in a particle or cell suspension and, by polarization of the particles, molecules and cells can be forced away from or toward the electrodes was investigated in detail by POHL in 1978 (POHL, H. P., Dielectrophoresis, Cambridge Press, Cambridge 1978) and established in patents such as U.S. Pat. No. 4,390,403.
These forces which are called dielectrophoresis may have both attracting (positive dielectrophoresis) and repelling (negative dielectrophoresis) effects. The phenomenon is utilized not only for the collection of dirt particles in macroscopic filters but also for the collection and separation of cells and microparticles in microstructures, to be sure until now only with limitations for the following reason:
(i) Electrodes were used in the macroscopic range and, miniaturized down to a few micrometers, and also were generated on planar surfaces. The high frequency electrical fields decoupled in the liquid then penetrate with almost the same field intensity through the entire cell resulting in a high stress on the objects (cells and particles), and very high excitation voltages are necessary (a few V up to a few 100 V). PA1 (ii) The electrodes are still so large that cells can be deposited on them although the field is switched on, since they no longer detect neighboring electrodes on the wider electrodes so that the sought effect that is is nullified. This problem arises, for instance, in WO 91/11262 (P & B Sciences Ltd.) where an electrode array is utilized which may have a chamber shape (cf. FIG. 1B there) but its size and dimensions are not adapted to the particles influenced. This Publication rather deals broadly with the sizes and shapes of "nonuniform magnetic fields" and their effect on chemical reactions between the cells. PA1 (iii) Cells or particles coming into contact with electrodes or directly attracted by them are changed irreversibly because of the metal/cell surface reaction.
High frequency traveling waves generated by electrical signals were utilized by MELCHER for pumping oils (MELCHER, J. R., The physics of fluids, 9:1548-1555, 1966). Toward the end of the 1980's and in the early 1990's this principle could also be realized in microchannels by means of electrode structures prepared by semiconductor technology. The principle is based on stabilization of a temperature gradient and generation of phase shifted space charges. Here also the width of the electrodes was a few 10 .mu.m (FUHR, G. et al., MEMS 92, Proceedings, 1992).
The fact that particles and cells can be selectively moved by means of traveling electrical fields was demonstrated by MASUDA (MASUDA, S., IEEE Transaction on Industry Applications, 24, 217-222, 1988) and was expanded in 1991 to include high frequency traveling waves (FUHR, G. et al., MEMS 91, Proceedings, 259-264, 1991). The purpose of this planar arrangement was to move individual cells in microchannel systems with the goal of cell separation as explained in more detail in WO 93/3850 (Fraunhofer-Gesellschaft).